Project Summary Multiple Sclerosis (MS) is a neuroinflammatory disorder characterized by immune attack of the myelin sheaths found in neurons of the central nervous system. Approaches that support or enhance endogenous myelin repair are vital to find new ways to treat MS, especially in its progressive phase. The mechanisms that drive the timing and specificity of oligodendrocyte myelination are not well understood. Seminal work has shown that oligodendrocyte progenitors receive synapses from neurons. We hypothesize that these connections are important both for correct myelination of neurons during development and for myelination during plasticity or after injury. We will utilize viral monosynaptic circuit tracing as a mean of analyzing these neuroglial connections in development, and to examine myelination and neuronal-glial connectivity after altering neural activity.